IDBR: Collaborative Research: Development of a Time-Resolved Photon-Counting Imager for Biology

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This is one of two awards supporting a collaborative project aimed at development of a new time-resolved single-photon imager optimized for ultrahigh sensitivity fluorescence spectroscopy and microscopy. The detector will be capable of registering individual (single) photons with high quantum efficiency and time resolution, and with high spatial resolution in two-dimensions (2D) at high-count rates. The instrument will be suitable for imaging and spectroscopy of single molecules, molecular complexes and macromolecules in living cells and tissues with increased sensitivity, signal-to-noise ratio and signal-to-background ratio, while providing multi-parametric, high information content from each detected photon (2D position, microscopic and macroscopic time of arrival with respect to an excitation by a train of short laser pulses, or wavelength and polarization anisotropy). The device has been dubbed the "H33D detector" for High-spatial resolution, High-temporal resolution and High count-rate 3-Dimensional detector. Targeted detector performance is: (i) quantum efficiency (QE) of 35 % @ 600nm. (ii) spatial resolution of 50 um x 50 um, allowing at least 256 x 256 resolution elements (pixels), (iii) temporal resolution of 150 picoseconds, and (iv) maximum count rate of 100 kHz per single pixel and 5 MHz over the whole detector. The development of the H33D detector comprises two complementary aspects: 1) a new detector design based on an initial prototype, and 2) new biological imaging and spectroscopy applications. The new detector design consists of a fast GaAs photocathode mounted in front of a stack of microchannel plates and a cross-strip anode. The readout electronics will be designed, built and tested by one of the collaborating groups. The other collaborating group will build the optical instrumentation and software needed for it. Two instruments will be built; the first, a non-optimized prototype, will be installed initially in a campus shared-use facility at UCLA, and eventually transferred to the California NanoSystems Institute Advanced Light Microscopy/Spectroscopy Shared Facility. Through these placements, the instrument will be available for use by a number of independent investigators and students. The experience gained from such use will be helpful in development of a second, more optimized instrument. Broader impacts of the project derive from the involvement of students in instrument construction and testing, and the availability of the instrument by a large number of investigators in a shared facility.